POLYMER-BASED STRATEGIES FOR THERAPEUTIC DELIVERY TO BACTERIAL BIOFILMS

Bacterial infections are emerging threat to public health. Antibiotics once provided front-line treatments to bacterial infections; however, bacteria adapted to resist antibiotics through drug resistance mechanisms and biofilm formation. In this dissertation, I describe polymer-based strategies for therapeutic delivery as treatments of bacterial biofilm infections. Initially, I developed a functional polymer for delivering hydrophobic carvacrol (the primary constituent of oregano oil) to the bacterial biofilms. This strategy incorporates a cross-linking strategy to fabricate a robust yet biodegradable nanoemulsion, improving antimicrobial activity of carvacrol and overcoming antimicrobial resistance development. Next, I demonstrated that this functional polymer-based emulsion platform provides a general and flexible strategy that improves the antimicrobial activity of a library of phytochemicals including eugenol, linalool, methyl eugenol, p-cymene, (+)-limonene, and α-pinene against the bacterial biofilms. In this follow up study, I also showed that encapsulating low log P phytochemicals effectively eliminates biofilms while demonstrating low cytotoxicity against mammalian fibroblast cells. In a related system, I worked with an antimicrobial nanoemulsion composed of all nature-derived materials. This antimicrobial platform uses gelatin stabilized by photocrosslinking with riboflavin (vitamin B2) as a photocatalyst, and carvacrol as the active antimicrobial. The engineered nanoemulsions demonstrate broad-spectrum antimicrobial activity towards drug-resistant bacterial biofilms and significantly expedite wound healing in vivo. Additionally, these nanoemulsions are particularly suitable to probe the interaction between nanomaterials and bacteria within the biofilm matrix. I have generated penetration profiles of nanoemulsions with varied surface charges to a bacteria biofilm using synthetic polymers and quantitative techniques. Finally, this dissertation includes a preliminary study of polymer encapsulation of bacteriophages for the treatment of bacterial biofilms. I have demonstrated that the polymer-bacteriophage nanoassembly improves antimicrobial activity of the bacteriophage against biofilms. In summary, this dissertation provides evidence that our polymer delivery strategy improves the antimicrobial efficacy of encapsulated therapeutics against bacterial biofilms.